the cause of this tragic disease and had traced it to tiny changes in the genes for collagen. Collagen is the most important and abundant protein in bones and it supports them in much the same way as steel rods strengthen reinforced concrete. It made sense that if collagen failed because of a fault in the gene, the bones would break. The research involved finding out a lot about the way collagen and its genes varied in the general population â and it was through this work that, in 1986, I came to meet Robert Hedges.
Robert runs the carbon-dating laboratory for archaeological samples in Oxford. He had been thinking about ways of getting more information from the bones that passed through his lab, aside from just dating them by the radiocarbon method. Collagen is the main protein not only in living bones but also in dead ones, and it is the carbon in the surviving collagen that is used to date them. Robert wondered if there was any genetic information in these surviving fragments of ancient collagen, so he and I put together a research proposal to study them. Collagen, being a protein, is made of units called amino-acids, arranged in a particular sequence. As we shall see in the next chapter, the sequence of amino-acids in collagen, and all other proteins for that matter, is dictated by the DNA sequence of their genes. We hoped to discover the DNA sequence of the ancient collagen genes indirectly by determining the order of amino-acids in the fragments of protein that survived in Robertâs old bones. We advertised for research assistants several times but got no response at all. We would have expected a flood of applications for a regular genetics post, and put this zero interest down to the unusual nature of the project. Disappointingly few scientists want to venture from the mainstream field of research at an early stage of their careers. For us, this lack of a recruit meant we had to put back the start of the project by a year. Although very frustrating at the time, the delay proved to be a blessing in disguise â because, before the project got going, news came in of a new invention. A US scientist in California called Kary Mullis had dreamed up a way of amplifying tiny amounts of DNA â under perfect conditions, as little as a single molecule â in a test tube.
One warm Friday night in 1983 Mullis was driving along Highway 101 by the ocean; according to his account of events, âthe night was saturated with moisture and the scent of flowering buckeyeâ. As he drove, he was talking to his girlfriend, seated beside him, about some of the ideas he had been pondering to do with his work at a local biotech company. Like everyone else in the genetic engineering business, he was making copies of DNA in test tubes. This was a slow process because the molecules had to be copied one at a time. DNA is like a long piece of string, and the copying started at one end and finished at the other. Then it started at the beginning again and you got another copy. He was talking out loud about this and suddenly realized that if, instead of starting the copying at one end only, you started at both ends you would start what would effectively be a sustainable chain reaction. You would no longer just be making copies of the original but copies of copies, doubling the number at every cycle. Now, instead of two copies after two cycles and three copies after three cycles, you would double up after each cycle, producing two, four, eight, sixteen, thirty-two, sixty-four copies in six cycles instead of one, two, three, four, five and six. After twenty cycles you would have not just twenty copies but a million. It was a real âEurekaâ moment. He turned to his girlfriend to get her reaction. She had fallen asleep.
This invention, for which Kary Mullis rightly won the Nobel Prize for Chemistry in 1993, genuinely revolutionized the practice of genetics. It meant that you could now get an unlimited amount of DNA to work